Overexpression of EGFR and c-MET in Triple Negative Breast Cancer Is Associated with Poor Prognosis
Agnieszka K Witkiewicz, Rebecca L Lipinski, Charalambos Solomides, Stephen Peiper. Thomas Jefferson University, Philadelphia, PA
Background: Triple negative breast cancer (TNBC) accounts for 10-20% of all breast cancers and is one of the subtypes associated with a poor prognosis. Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor that plays a role in cell proliferation and migration, is expressed in 40-60% of TNBC. C-MET is a proto-oncogene that is associated with tumor growth and metastasis and has been shown to correlate with EGFR expression in breast cancer cell lines. Recently it has been postulated that c-MET may play a key role in the resistance to EGFR tyrosine kinase inhibitors. The goal of this study was to analyze the expression and prognostic significance of EGFR and c-MET in patients with TNBC.
Design: Tissue microarrays with 186 triple negative breast cancers were used in the study. EGFR and c-MET expression was evaluated by immunhistochemistry. EGFR and c-MET were scored as 0 (no staining seen, or staining in <10% of tumor cells), 1+ (weak and incomplete staining in >10% of tumor cells), 2+ (weak to moderate complete membrane staining seen in >10%), or 3+ (moderate to strong complete membrane staining in >10%). Positive score was defined as 2+ or 3+. Overall survival was assessed using Kaplan-Meier analysis.
Results: Staining for both markers could be evaluated for 169 cases. Of these samples, 80 (47%) were negative and 89 (53%) positive for EGFR. 127 (75%) samples were c-MET negative and 42 (25%) were c-MET positive. When analyzed in combination, 27 (16%) samples were EGFR+c-MET+, 65 (39%) EGFR- c-MET-, 62 (37%) EGFR+ c-MET-, and 15 (8%) were EGFR- c-MET+. Combined expression of EGFR and c-MET was associated with a decreased survival (p=.0162).
Conclusions: Combined EGFR and c-MET overexpression is associated with decreased survival time in triple negative breast cancer patients.
Monday, March 19, 2012 1:00 PM
Poster Session II # 61, Monday Afternoon